Browse Articles

A self-supervised machine learning pipeline for extracting information from live cell images at multiple doses and timepoints

Abstract Live cells are complex information-processing systems that continuously sense their environment and respond dynamically. However, conventional endpoint assays typically require fixation or cell destruction and fail to capture complex temporal changes. Live brightfield imaging offers a scalable, label-free solution that remains underutilized due to particularly low contrast, acute technical batch sensitivity, and the limited availability of robust computational methods for this modality. Leveraging recent self-supervised learning developments, we introduce Live Cell Dynamics (LCD), a novel end-to-end transformer-based pipeline, using novel plane-agnostic augmentation (treating different focal planes as views of the same state) and incorporating cross-batch sampling. LCD addresses brightfield modality challenges and extracts subtle dose- and time-dependent live cell states. Through systematic ablation we evaluate each self-supervised training innovation on a single cell line, measuring phenotypic activity (mean Average Precision) and Mechanism of Action (MoA) classification (F1-score), with 189 compounds in pre-training and 81 in holdout spanning ten MoAs. Our approach outperforms ablated baselines across all doses and timepoints for activity and MoA classification, enables compound polypharmacology detection from multi-dose/timepoint profiles, and supports unsupervised nuclei detection and counting. It leads to training foundation models from continuous live brightfield imaging to detect subtle live cell state changes, enabling scalable, cost-effective drug development.

The ro-vibrational spectroscopy of H2NCO (2A′) and HNCOH and the peculiar case of their isomers <i>cis</i> - and <i>trans</i> -HNCHO

While quantum chemical treatment of the prebiotic, astrochemically relevant H2NCO molecule’s rotational constants and fundamental vibrational frequencies produces exceptionally accurate values, the cis-HNCHO isomer is more of a challenge to standard electronic structure methods. The trans-HNCHO conformer is well-behaved like H2NCO due to the nature of the local potential energy surface, but the zero-point vibrational energy of the torsional motion is significantly greater than the barrier, implying that this isomer cannot be observed. The 2.6 kcal mol−1 lower-energy cis-HNCHO conformer showcases a small pseudo-Jahn–Teller distortion about the HNCO torsion coordinate at planarity. This produces a challenging environment for the quartic force field (QFF) treatment of the rotational and vibrational spectroscopic data. Even so, the accuracy of the H2NCO spectroscopic constants from this explicitly correlated coupled cluster theory QFF implies that similar accuracy should be present for the mathematically well-behaved trans-HNCHO, which exists in a shallow but true minimum. The constants computed herein may allow for a more detailed search of experimental rotation spectra for cis-HNCHO, which would provide reference data necessary for potential searches for this molecule in space. Rotational constants are also provided for the four conformers of HNCOH, and the fundamental vibrational frequencies in the range of James Webb Space Telescope observation are provided for all isomers in order to allow for the possibility of multiple wavelength observation of this family of molecules, which may play a role in the molecular origins of life.

Survival after spinal surgery for metastases in men with castration-sensitive vs castration-resistant prostate cancer: a nationwide register-based study

Abstract This nationwide register-based cohort study examined the association between castration status and postoperative survival in men who had undergone surgery for spinal metastases from prostate cancer. Bone metastases are common in prostate cancer, with the spine being the most frequent site. Using data from the Swedish Spine Register (Swespine) and Prostate Cancer Database Sweden (PCBaSe), 306 men with prostate cancer who underwent spinal surgery were identified. In total, 81 were categorized as castration-sensitive and 225 as castration-resistant disease at the time of spinal surgery. Postoperative survival was estimated using Kaplan–Meier analysis and compared with the log-rank test. Multivariable Cox regression was used to adjust for potential confounders. Median survival after surgery was significantly longer in men with castration-sensitive prostate cancer (33 months, IQR 15–55) compared to those with castration-resistant disease (8 months, IQR 5–31; p &lt; 0.001). Castration-sensitive status was independently associated with a lower risk of death (hazard ratio 0.29, 95% CI: 0.20–0.41). These findings indicate that castration sensitivity is a strong prognostic factor for survival after surgery for spinal metastases from prostate cancer and should be considered in surgical decision-making.

Machine-learning accelerated density-explicit polymer field theory simulations

Recently, the density-explicit framework, which describes the thermodynamic properties of multicomponent polymer systems as functionals of both auxiliary and density fields, has attracted growing interest in polymer field theory simulations. This is due to the flexibility of the framework in accommodating various forms of intermolecular potentials, and in particular, the easy generalization to many-body interactions beyond pair potentials. However, numerical simulations based on the formalism are generally more expensive owing to the increased number of fields, compared to the conventional auxiliary field framework. In this work, we develop deep neural networks with efficient low-dimensional and largely local feature representations that are applicable across different spatial resolutions and dimensions to accelerate polymer field theory simulations based on this framework. Our results may serve as a stepping stone toward accurate and efficient prediction of the phase behavior of complex block copolymer mesophases, as well as a blueprint for developing machine learning-assisted field theoretic simulation tools for the computational study of polymers and soft matter systems more broadly.

Machine learning guided Box–Behnken design optimized green synthesis of carbon nitride nanoparticles with antioxidant activity and low SH-SY5Y cytotoxicity

An accurate and efficient NPT ensemble molecular dynamics simulation method

The accuracy of the NPT ensemble is important for obtaining accurate biomolecular dynamics and thermodynamic properties in molecular dynamics simulations. Although considerable effort has been devoted to improving its accuracy, most studies have not been rigorously validated. We introduce a novel NPT ensemble method that meticulously optimizes the critical components that significantly improve accuracy and efficiency, especially in pressure regulation. In particular, our method (i) incorporated the Martyna–Tobias–Klein correction terms into the equations of motion for the desired NPT partition function, (ii) utilized the Langevin dynamics algorithm for barostat equilibration to reduce mass-dependent ringing effects, (iii) integrated the barostat using the BAOAB scheme to ensure minimal error and high stability, and (iv) employed molecular pressure to optimize the constraint calculation. Tests showed that our NPT ensemble method achieved accurate and well-converged pressure and temperature control in both protein solutions and pure water systems.

Runoff Potential Index (RPI): 3D modelling of surface-driven hydrological dynamics for drought resilience

Combined effects of polymer/substrate interaction and chain adsorption on the <i>T</i> g-confinement effect of supported thin polystyrene films

The thickness dependence of the glass transition temperature (i.e., the Tg-confinement effect) and its molecular weight (Mw) dependence in polystyrene (PS) thin films supported on attractive substrates are systematically investigated as a function of annealing time at 423 K. It is demonstrated that the shift in Tg (ΔTg= Tgfilm − Tgbulk) exhibits a consistent linear dependence on the degree of adsorption (hads/hadseq) across PS films with different Mw on a given substrate, described by ΔTg = khads/hadseq + b. The slope k is found to be independent of the substrate, whereas the intercept b increases with the increasing polymer/substrate interactions due to additional losses in interfacial free volume arising from more densely packed adsorbed conformations. In addition, the dependence of the Tg-confinement effect on Mw is observed under non-equilibrium adsorption conditions caused by Mw-dependent adsorption kinetics. These results provide physical insights into how chain adsorption, which is strongly modulated by polymer/substrate interactions, affects the Tg-confinement effect in polymer thin films.

Plasma growth differentiation factor-15 is associated with cardiovascular events in patients hospitalized for acute exacerbation of COPD

Anisotropic self-assembly of soft particles induced by elliptically polarized AC electric fields

Attractive dipole interactions can be induced between equally charged soft nanoparticles under the influence of AC electric fields. The combination of charge repulsion and dipole attraction, along with different screening responses from an underlying electrolyte, leads to complex aggregations ranging from chain-like formation for linear polarizations to isotropic planar structures in the case of circular polarizations. In this work, we analyze the role of varying field anisotropies in these self-assembled structures. To this end, the formalism previously developed for the coarse-grained interactions of soft particles in the presence of linear [T. Colla et al., ACS Nano 12, 4321–4337 (2018)] and circular [M. Reich et al., Soft Matter 21, 1516–1528 (2025)] field polarizations is naturally extended to incorporate elliptical polarizations of arbitrary asymmetries. A rich variety of self-assembly formations is found at intermediate field anisotropies, thus bridging the gap between linear- and circular-field-induced self-assembly scenarios.

A multi-scale dual-stream fusion network for high-accuracy sEMG-based gesture classification

Erratum: “Submatrix and GPU-accelerated implementation of density matrix tight-binding” [J. Chem. Phys. 163, 132501 (2025)]

Bone mesenchymal stem cells-derived exosomal miR-509-5p promotes osteogenic differentiation by targeting SFRP1 and activating the Wnt/β-catenin pathway

Biomarker <i>δ</i> ¹³ C values record consistent savanna vegetation and variable alkalinity of Lake Olduvai during Pleistocene wet/dry cycles

Climate records for the early Pleistocene in eastern Africa aid reconstruction of the ecology and landscapes occupied by hominins. Environmental changes associated with alternating wet/dry cycles during this critical interval in hominin evolution are recorded in isotopic profiles from lake sediments from Olduvai Gorge. The Olduvai Gorge Coring Project targeted the depocenter of Paleolake Olduvai, recovering a stratigraphic succession between the Bed I Basalt (~1.90 Ma) and Tuff IF (~1.80 Ma) datums that span hominin fossil horizons in nearby outcrops. Lacustrine claystones from the lower part of this interval are characterized by high C org (avg. 2.5 %). They display variations in δ 13 C org reflecting temporal changes in organic matter (OM) sources. Stratigraphic profiles for n -alkane δ 13 C values derived from plant waxes are consistent throughout wet/dry cycles indicating stability in savanna vegetation, refuting evidence for increased C 4 grasses during drier intervals. δ 13 C values for n -alkanes derived from aquatic macrophytes and for algal biomarkers increase during drier episodes, reflecting use of bicarbonate as a carbon source triggered by enhanced lake alkalinity. δ 13 C org profiles reflect variations in inputs of terrestrial vs. aquatic OM during wet/dry cycles, which are mirrored by δ 13 C values for hop-17(21)-ene derived from heterotrophic bacteria utilizing sedimentary OM. The δ 13 C records from Paleolake Olduvai sediments show temporal changes in OM sources rather than shifts in the proportion of C 3 and C 4 vegetation, indicating that precession-driven climate cycles primarily affected lake environments and associated aquatic resources. Thus, intervals of high climate variability did not necessarily cause changes in savanna vegetation affecting hominin habitats.

Exclusive breastfeeding and postpartum depression: A protective association that is not modified by feeding intentions

Approximately 13% of women in the United States (U.S.) experience postpartum depression (PPD), a mood disorder that negatively affects maternal and infant wellbeing. Breastfeeding may protect against PPD and breastfeeding intentions may moderate this relationship. This study examined the association between breastfeeding status and PPD symptoms and whether exclusive breastfeeding intentions moderate this relationship in low-income women in the U.S. We utilized data from the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) Infant and Toddler Feeding Practices Study-2, a longitudinal cohort study of caregiver feeding practices and nutrition outcomes among children enrolled in WIC. Exclusive breastfeeding intentions were measured prenatally; breastfeeding status at 1 month; and PPD symptoms at 3 months postpartum using the Edinburgh Postpartum Depression Scale (elevated PPD symptoms defined as EPDS ≥ 10). We conducted logistic regression to examine the association between breastfeeding status and elevated PPD symptoms. We stratified the analysis by exclusive breastfeeding intention-status groups to assess moderation. Adjusted models controlled for self-reported maternal ethnicity, annual household income, and smoking during pregnancy. The analytic sample included 2,022 mothers who identified their race as Black or African American (20.7%), White (58.8%), or other (20.6%), and their ethnicity as Hispanic (48.1%) or non-Hispanic (51.9%). The majority were ≥20 years old (88.2%), not married (68.2%), and had a high school education or less (62.7%). Compared to mothers who exclusively breastfed, those who combination fed (AOR, 2.03; 95% CI, 1.23–3.40) or exclusively formula fed (AOR 2.03; 95% CI 1.16–3.42) at 1 month had higher odds of elevated PPD symptoms. Exclusive breastfeeding intentions did not moderate this relationship. While exclusive breastfeeding was associated with a lower likelihood of experiencing elevated PPD symptoms, the majority of participants did not meet their exclusive breastfeeding intentions, highlighting the need for enhanced breastfeeding support.

Food absence is a cue for metamorphosis in the solitary bee <i>Megachile rotundata</i> through a conserved physiological mechanism

The timing of metamorphosis in insects determines adult body size and influences aspects of fitness including flight performance and fecundity. The regulation of metamorphosis has been well studied in model insects but determining the cue that initiates the physiological shift toward metamorphosis in other insects has been challenging. In most insects, the critical weight is a cue to initiate metamorphosis. Our goal was to determine the cue for metamorphosis in the solitary bee Megachile rotundata and to characterize the physiological mechanisms initiated by this cue. Larval bees were fed ad libitum (also termed “fed”) or had all food removed (also termed “starved”). We measured the time to initiate metamorphosis, juvenile hormone (JH) titers, and the abundance of transcripts involved in the endocrine response to metamorphosis. We experimentally manipulated JH by topically applying precocene, which interrupts JH production. We found that M. rotundata does not have a critical weight and that starvation through the removal of food triggered the initiation of metamorphosis. Food removal was associated with low JH titers, and the application of precocene mimicked the response to food absence. Food removal decreased transcripts associated with JH production, and increased transcripts involved in ecdysone synthesis and insulin/TOR signaling. Food absence is an ecologically relevant cue for a M. rotundata larva, which is provisioned a finite amount of food and is unable to forage for additional food. Despite having food removal as a cue for metamorphosis, the physiological mechanisms associated with metamorphosis are similar to those found in other insects.

Attachment-related perceptions of life events

This study explored how attachment orientations are associated with perceptions of life events. Although there is evidence that life and relationship contexts have the potential to alter attachment anxiety and avoidance across the lifespan, life events often exert only modest or transient effects on attachment orientations. The current study ( N  = 1943; M age  = 19.61; 74.1% women) examined associations between attachment orientations, perceptions of whether life events might engender personality changes, and perceptions of 20 hypothetical life events across nine dimensions (e.g., emotional significance, impact, control). Individuals high in attachment anxiety perceived life events as more challenging, impactful, emotionally significant, unpredictable, negative, and likely to alter their worldview and negatively affect their social status—viewing them as likely to induce personality changes. Conversely, individuals high in attachment avoidance minimized life events’ potential effects, perceiving them as less significant and less likely to alter personality. Future research could further examine whether attachment orientations shift in response to life events according to perceived event characteristics.

Evaluating inbreeding and assessing the risk of outbreeding depression in genetic rescue using whole-genome sequence data

Restoring genetic diversity through assisted migration is increasingly recognized as a crucial strategy to counteract inbreeding depression and boost genetic variation in small and fragmented populations yet concerns about outbreeding depression often hinder its application. We propose a genomics-informed update to an existing framework enabling a more precise assessment of outbreeding depression risk and genetic rescue feasibility. We apply this approach to a butterfly species—the marsh fritillary ( Euphydryas aurinia )—which has faced severe range contractions and near-extinction in Denmark. We identify substantial inbreeding in the investigated populations (F ROH approaching 40%), historical gene flow, recent divergence times between populations, and low likelihood of local adaptation. Together, these results provide an example where genetic rescue could be undertaken successfully by transplanting individuals across populations with minimal outbreeding depression risks. Despite working with a scaffold-level assembly and moderate sample sizes, our analyses provide robust insights into population dynamics, demography, and local adaptation, demonstrating that even imperfect genomic data can inform conservation strategies. By refining an existing framework, we illustrate how genomics can enhance genetic rescue efforts and guide decision-making for threatened species. Our approach provides a scalable model for integrating genomic data into conservation management, advancing the use of evolutionary and conservation genetics principles in mitigating biodiversity loss.

Attribution of credit in acknowledgements: The case of systematic reviews in medicine

Scientific research increasingly benefits from the work of non-author contributors, who engage in valuable activities but do not meet authorship criteria. The support of these contributors remains invisible unless it is recorded in acknowledgement texts, which has implications for research transparency and fair attribution of credit. While much research has examined authorship, acknowledgements have been largely neglected. We explore whether acknowledgements omit deserving contributors and the heterogeneity of omissions by gender and race. We focus on the medical field, which is often a forerunner in terms of attribution of credit, and consider acknowledgements in Cochrane systematic reviews. These reviews are governed by unique guidance that allows us to determine whether a contributor receives due credit. We find that as many as 40% of the eligible reviews in our sample (those that should have acknowledged prior authors) did not appropriately acknowledge non-author contributors. Non-White contributors were more likely to be missing from the acknowledgements. This disparity cannot be explained by non-White contributors being more likely to perform minor/technical review tasks or being in predominantly White research teams or teams led by White scientists. Instead, the effect is driven by geographical disparities, with non-White contributors being more likely to be deprived of due acknowledgements in reviews from Asia, South America and Africa. Furthermore, in most cases, all contributors were omitted from the acknowledgements, rather than specific contributors being excluded alone. Taken together, we provide novel evidence of some racial disparities in credit attribution in acknowledgements. Reassuringly, these appear to be driven by poor acknowledgement practice and geographical disparities rather than targeted exclusion.

Enhanced insulin signaling via circulating ATG7: A potential therapeutic strategy for diabetes

Diabetes and insulin resistance (IR) remain major global health challenges, underscoring the need for novel therapeutic strategies. Here, we identify an autophagy-independent role of circulating autophagy-related gene 7 (ATG7) in metabolic regulation. Circulating ATG7 enhances insulin sensitivity and glucose homeostasis by directly interacting with IRS1 and modulating insulin signaling (IS) through liver–muscle crosstalk. Mechanistically, ATG7 binds to IRS1, promoting its activation and the propagation of downstream IS. Notably, we identify an ATG7-derived peptide (Aap2) that recapitulates ATG7’s insulin-sensitizing effects and improves glycemic control in both Type 1 and Type 2 diabetic mouse models. These findings establish ATG7 as a key regulator of IS and suggest that targeting ATG7 may represent a promising therapeutic approach for IR and diabetes.